Prognostic validation and refinement of a classification system for extent of resection in glioblastoma: A report of the RANO <i>resect</i> group.
Authors: Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stefanie T. Jünger, Nico Teske, Michael Weller, Roberta Ruda, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Stefan Grau, Annette M. Molinaro, Mitchel S. Berger, Susan Marina Chang, Martin J. Van Den Bent, Joerg Tonn
Journal: Journal of Clinical Oncology (2022)

2003 Background: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system for glioblastoma was previously proposed based upon the absolute residual contrast-enhancing (CE) tumor (in cm 3 ) and the relative reduction of CE tumor (in percentage) on postoperative MRI. Class 0 was defined as ‘supramaximal CE resection’ (also including removal of non-CE tumor), class 1 as ‘maximal CE resection’, class 2 as ‘submaximal CE resection’, and class 3 as ‘biopsy’. We aimed to (I) explore the prognostic utility of the proposed classification system and (II) define how much non-CE tumor needs to be removed to translate into a survival benefit. Methods: An international Response Assessment in Neuro-Oncology (RANO) group was formed, entitled RANO resect. The members of the RANO resect group retrospectively searched the databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma. Clinical characteristics, volumetric information from pre- and postoperative MRI, and outcome were collected. Kaplan-Meier survival analysis and log-rank test were applied to calculate survival, and Cox’s proportional hazard regression model to adjust for multiple variables. Significance level was set at p ≤ 0.05. Results: We encountered 1021 patients with newly diagnosed glioblastoma, including 1008 IDHwt patients. 744 IDHwt patients were treated with radiochemotherapy per EORTC 26981/22981 following surgery. Among such homogenously treated patients, higher extent of resection was favorably associated with outcome: patients with ‘maximal CE resection’ (class 1) had superior outcome compared to patients with ‘submaximal CE resection’ (class 2) or ‘biopsy’ (class 3) (median OS: 20 versus 16 versus 10 months; p = 0.001). Similar findings were made when assessing progression (median PFS: 9 versus 8 versus 5 months; p = 0.001). Extensive resection of non-CE tumor (≥60% of non-CE tumor removed and ≤5 cm 3 residual non-CE tumor) provided an additional survival benefit in patients with complete CE resection (class 1), thus defining class 0 (‘supramaximal CE resection’) (median OS: 29 versus 20 months; p = 0.003). Smaller pre-operative tumor volumes were associated with larger extent of resection. The favorable prognostic effect of CE resection was conserved in a multivariate analysis when stratifying for molecular and clinical markers including pre-operative tumor volume and MGMT promotor status ( p = 0.001). Conclusions: The proposed classification system for extent of surgery in glioblastoma is highly prognostic and may serve for stratification and design of clinical trials. Removal of non-CE tumor beyond the CE tumor borders translates into additional survival benefit in glioblastomas, providing a rationale to explicitly denominate such a 'supramaximal CE resection.'